A study presented at the 2015 meeting of the American Society of Clinical Oncology (ASCO; 29 May–2 June, IL, USA) has reported that immunotherapy with the anti-PD-1 antibody pembrolizumab demonstrated efficacy in one in four patients diagnosed with recurrent or metastatic head and neck cancer. These findings could change the way head and neck cancer is treated, as pembrolizumab could meet the need for more efficacious therapies in this common type of cancer.
The results indicated that pembrolizumab treatment decreased the size of tumors by 30% or more in 24.8% of a 132 patient study group. Tanguy Seiwert from the University of Chicago (IL, USA) commented: “The efficacy was remarkable, roughly twice as good as any drug combination in our arsenal.”
In this study, 132 patients diagnosed with recurrent or metastatic squamous cell carcinoma of the head and neck were administered with a 200 mg infusion of pembrolizumab every 3 weeks. Unlike a previous study – presented at ASCO in 2014 – this cohort was not selected for PD-L1 expression, with 59% of the patients enrolled already having received two or more previous therapies. Seiwert continued: “Our 25% response rate may underestimate the benefit in patients. We know from other disease entities such as lung cancer – where the experience with immunotherapy is broader – that patients who have disease stabilization or even pseudo-progression may benefit in ways that translate into longer survival.”
This study demonstrates that pembrolizumab is approximately twice as effective as the current preferred treatment, which utilizes platinum-based chemotherapy and the EGFR inhibitor cetuximab.
Of the patients who received pembrolizumab, 56% displayed tumor shrinkage, and the objective response rate was 24.8% (26.3% in HPV-negative patients and 20.6% in HPV-positive patients). Pembrolizumab was reported to be well tolerated, with less than 10% of individuals experiencing serious side effects such as fatigue, rash and pruritus. More serious immune-related side effects such as grade 3 pneumonitis and colitis were reported in three patients.
Seiwert continued: “In this study, pembrolizumab was active across a wide range of patient subgroups including HPV-associated and HPV-negative tumors. Overall, 56% of patients experienced a measurable decrease in the size of their tumors.”
The checkpoint inhibitor demonstrated similar levels of activity in HPV-associated and HPV-negative tumors. This is in contrast to the EGFR inhibitors, which appear to be less effective in HPV-positive tumors.
Seiwert concluded: “This may have the potential to prolong survival for a large proportion of our patients. Immunotherapy has been very well tolerated by our patients and serious side effects have been quite uncommon. We hope this approach will change the way we treat head and neck cancer.”
A related study by Seiwert and colleagues – also presented at ASCO15 (abstract #6017) – has reported that an experimental test, which was applied to an earlier cohort of head and neck cancer patients treated with pembrolizumab, was able to predict which patients were unlikely to benefit from PD-1/PD-L1-targeting agents, with a negative predictive value of 95%.
Seiwart commented: “This assay is quick and reproducible. The high negative predictive value may help us select out patients who may not benefit from immunotherapy.”
Going forward, two Phase III studies – currently in process – are investigating the efficacy of pembrolizumab compared with standard treatment in individuals with recurrent or metastatic head and neck cancer. Additional Phase III studies investigating the anti-PD-1 antibody, nivolumab and the anti-PD-L1 antibody MEDI4736 in patients with head and neck cancer are also ongoing.